The gingival epithelia form a barrier against oral pathogens and their toxic products, but little is known about the mechanisms that mediate these functions or their failure in periodontal disease. Cell-cell and cell-substrate interactions are required for epithelial function and in many cases keratinization also plays a role in barrier formation. Of the three gingival epithelia (junctional, sulcular and oral epithelium), only the latter is keratinized. Barrier function in the junctional and sulcular epithelia must, therefore, be more dependent on cell-cell and cell- substrate adhesion. The junctional epithelium is unique in that neutrophils migrate through it and it is a site of periodontal infection. Given the above differences, it seems likely that interactions between cells in the junctional and sulcular epithelia will differ from each other and from those in the keratinized oral gingival epithelium, and that the expression of cell-cell adhesion molecules (CAMs) will differ between the three gingival epithelia. The cadherins are one of several families of CAMs. In other systems cadherins have been shown to be crucial for the organization of epithelia, for epithelial stratification and for the maintenance of epithelial barrier function. I hypothesize that cadherins play equally important roles in gingival epithelia, and that cadherin expression differs between the gingival epithelia. In preliminary results I show that cadherins are present in the gingival epithelium. I propose to characterize in detail the expression of cadherins in normal and diseased human gingival epithelia and in oral epithelial cells grown in vitro using immunohistochemical, biochemical and molecular biological techniques, and to analyze the regulation of gingival cadherin expression. These studies should provide a new understanding of cell-cell interactions in the gingiva that participate in gingival epithelial barrier function. They may form the basis for new approaches to the prevention and/or treatment of periodontal disease.